The large scale solid phase synthesis of specific-sequence drugs, including antisense drugs, aptamers, ribozymes, nexamers, and others pose a series of problems which are not completely solved. Bench scale synthesis of these compounds is routine, as is gram-scale production in so-called "large scale" synthesizers. The development of compounds of this class as pharmaceuticals requires initially small scale synthesis for screening, intermediate scale synthesis for toxicological and pharmacological studies, and progressively larger production for more extended animal studies, and clinical trials. A large increment in scale of production is required if a drug is finally approved. Existing commercial synthesizers, used initially alone and then in batteries run continuously, and have allowed companies to reach Phase I clinical trials for most drugs, and to reach full production for drugs whose utilization will be small. However, for compounds which will require production in the range of tens of kilos to metric tons per year, there has been no path to bridge the gap between existing gram scale systems and projected large scale production. This proposal describes the development of a flexible solid phase synthesis system, each component of which can be scaled up to the kilogram-of-product range, the construction and testing of the components on a small scale, and a systematic plan for designing, evaluating, and producing a series of increasingly larger systems. PROPOSED COMMERCIAL APPLICATION: Maintaining world leadership in the production of new pharmaceuticals is important to the U.S. economy. The development of proprietary and efficient methods for the synthesis of new and promising classes of drugs - a potential product of this research - will assist in maintaining that leadership.